scholarly journals Chirality of β2-agonists. An overview of pharmacological activity, stereoselective analysis, and synthesis

2020 ◽  
Vol 18 (1) ◽  
pp. 628-647
Author(s):  
Čižmáriková Ružena ◽  
Valentová Jindra ◽  
Horáková Renáta
Keyword(s):  
Analytical Methods ◽  
Stereoselective Synthesis ◽  
Adrenergic Agonists ◽  
Chiral Drugs ◽  
Beta Agonists ◽  
Sympathomimetic Drugs ◽  
Stereogenic Centers ◽  
Analysis And Synthesis ◽  
Pure Enantiomer ◽  
Β2 Agonists

Abstractβ2-Agonists (β2-adrenergic agonists, bronchodilatants, and sympathomimetic drugs) are a group of drugs that are mainly used in asthma and obstructive pulmonary diseases. In practice, the substances used to contain one or more stereogenic centers in their structure and their enantiomers exhibit different pharmacological properties. In terms of bronchodilatory activity, (R)-enantiomers showed higher activity. The investigation of stereoselectivity in action and disposition of chiral drugs together with the preparation of pure enantiomer drugs calls for efficient stereoselective analytical methods. The overview focuses on the stereoselectivity in pharmacodynamics and pharmacokinetics of β2-agonists and summarizes the stereoselective analytical methods for the enantioseparation of racemic beta-agonists (HPLC, LC-MS, GC, TLC, CE). Some methods of the stereoselective synthesis for β2-agonists preparation are also presented.

scholarly journals Advances on Greener Asymmetric Synthesis of Antiviral Drugs via Organocatalysis

2021 ◽  
Vol 14 (11) ◽  
pp. 1125
Author(s):  
Everton M. da Silva ◽  
Hérika D. A. Vidal ◽  
Arlene G. Corrêa
Keyword(s):  
Pharmaceutical Industry ◽  
Antiviral Activity ◽  
Asymmetric Synthesis ◽  
High Mortality ◽  
Viral Infections ◽  
Mortality Rates ◽  
Chiral Drugs ◽  
Stereogenic Centers ◽  
Synthetic Routes ◽  
New Compounds

Viral infections cause many severe human diseases, being responsible for remarkably high mortality rates. In this sense, both the academy and the pharmaceutical industry are continuously searching for new compounds with antiviral activity, and in addition, face the challenge of developing greener and more efficient methods to synthesize these compounds. This becomes even more important with drugs possessing stereogenic centers as highly enantioselective processes are required. In this minireview, the advances achieved to improve synthetic routes efficiency and sustainability of important commercially antiviral chiral drugs are discussed, highlighting the use of organocatalytic methods.

scholarly journals Advances on Greener Asymmetric Synthesis of Antiviral Drugs via Organocatalysis

2021 ◽  
Author(s):  
Arlene Gonçalves Corrêa ◽  
Everton Machado da Silva ◽  
Herika Danielle Almeida Vidal
Keyword(s):  
Pharmaceutical Industry ◽  
Antiviral Activity ◽  
Asymmetric Synthesis ◽  
High Mortality ◽  
Viral Infections ◽  
Mortality Rates ◽  
Chiral Drugs ◽  
Stereogenic Centers ◽  
Synthetic Routes ◽  
New Compounds

Viral infections inflict many serious human diseases, being responsible for remarkably high mortality rates. In this sense, both the academy and the pharmaceutical industry are continuously searching for new compounds with antiviral activity, and in addition, face the challenge of developing greener and more efficient methods to synthesize these compounds. This becomes even more important with drugs possessing stereogenic centers as highly enantioselective processes are required. In this minireview, the advances achieved to improve synthetic routes efficiency and sustainability of important commercially antiviral chiral drugs are discussed, highlighting the use of organocatalytic methods.

scholarly journals Stereoselective Synthesis of Highly-Congested Tetralin-Fused Spirooxindoles with Hydroxyl Group: Net Oxygen Atom Induced Hydride Shift/cyclization Process.

2021 ◽  
Author(s):  
Dan Sakai ◽  
mizuki machida ◽  
Keiji Mori
Keyword(s):  
Reaction Mechanism ◽  
Nitrogen Atom ◽  
Oxygen Atom ◽  
Stereoselective Synthesis ◽  
Hydroxyl Group ◽  
Target Structure ◽  
Hydride Shift ◽  
Cyclization Process ◽  
Stereogenic Centers

Highly stereoselective synthesis of tetralin-fused spirooxindoles with two contiguous stereogenic centers. In the present reaction, not only [1,5]-hydride shift/cyclization process, but also replacemnt of nitrogen atom to oxygen atom ocurred smoothly to give target structure with hydroxy grop in good chemical yields with good to excellent diastereoselectivities (up to d.r. = >20:1). Investigation of the reaction mechanism suggested that this “atom-replacement” event ocurred via the iminium cation intermediates.

scholarly journals Lewis acid–catalyzed domino generation/[2,3]-sigmatropic rearrangement of ammonium ylides to access chiral azabicycles

2021 ◽  
Vol 7 (5) ◽  
pp. eabd5290
Author(s):  
Song Xi ◽  
Jiawei Dong ◽  
Haohua Chen ◽  
Qiuyan Dong ◽  
Jiao Yang ◽  
...  
Keyword(s):  
Density Functional ◽  
Stereoselective Synthesis ◽  
Experimental Studies ◽  
Reaction System ◽  
Density Functional Theory Calculations ◽  
Sigmatropic Rearrangement ◽  
Residual Water ◽  
Nitrogenous Compounds ◽  
Stereogenic Centers ◽  
Quaternary Stereogenic Centers

[2,3]-Sigmatropic rearrangement of ammonium ylides represents a fundamental reaction for stereoselective synthesis of nitrogenous compounds. However, its applicability is limited by the scarcity of efficient, catalytic, and mild methods for generating ammonium ylides. Here, we report silver-catalyzed domino generation/[2,3]-sigmatropic rearrangement of ammonium ylides, furnishing chiral azabicycles with bridgehead quaternary stereogenic centers in high enantiomeric purity (up to 99% ee). A combination of density functional theory calculations and experimental studies revealed that residual water in the reaction system is crucial for the mild reaction conditions by functioning as a proton shuttle to assist carbon-silver bond protonation and C2─H deprotonation to generate the ammonium ylide. This reaction has a broad application scope. Besides the diverse substituents, N-fused azabicycles of various ring sizes are also easily accessed. In addition to silver salts, this strategy has also been successfully implemented by using a stoichiometric amount of nonmetallic I2.

scholarly journals Stereoselective Synthesis of Highly-Congested Tetralin-Fused Spirooxindoles with Hydroxyl Group: Net Oxygen Atom Induced Hydride Shift/cyclization Process.

2021 ◽  
Author(s):  
Dan Sakai ◽  
mizuki machida ◽  
Keiji Mori
Keyword(s):  
Reaction Mechanism ◽  
Nitrogen Atom ◽  
Oxygen Atom ◽  
Stereoselective Synthesis ◽  
Hydroxyl Group ◽  
Target Structure ◽  
Hydride Shift ◽  
Cyclization Process ◽  
Stereogenic Centers

Highly stereoselective synthesis of tetralin-fused spirooxindoles with two contiguous stereogenic centers. In the present reaction, not only [1,5]-hydride shift/cyclization process, but also replacemnt of nitrogen atom to oxygen atom ocurred smoothly to give target structure with hydroxy grop in good chemical yields with good to excellent diastereoselectivities (up to d.r. = >20:1). Investigation of the reaction mechanism suggested that this “atom-replacement” event ocurred via the iminium cation intermediates.

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